Mild and nonracemizing conditions for Ullmann-type diaryl ether formation between aryl iodides and tyrosine derivatives

Article abstract of DOI:10.1021/jo0606960

CuI/N,N-dimethylglycine-catalyzed coupling reaction of L-tyrosine derivatives and L-phenylalanine-derived iodides in the presence of Cs ₂CO₃ works at 90 °C to provide the corresponding diaryl ether. Partial racemization occurs when N

Full text of DOI:10.1021/jo0606960

Mild and Nonracemizing Conditions for Ullmann-type Diaryl Ether
Formation between Aryl Iodides and Tyrosine Derivatives
Qian Cai, Gang He, and Dawei Ma*
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
madw@pub.sioc.ac.cn
ReceiVed April 1, 2006
CuI/N,N-dimethylglycine-catalyzed coupling reaction of L-tyrosine derivatives and L-phenylalanine-derived
iodides in the presence of Cs2CO3 works at 90 °C to provide the corresponding diaryl ether. Partial
racemization occurs when N-Boc- and N-Cbz-protected aromatic amino esters are used, while N-trityl-
and N,N-dibenzyl-protected aromatic amino esters give rise to coupling products without loss of optical
purity. Little racemization is also observed in cases of N-Boc- and N-Cbz-protected aromatic amino
acids as substrates. But their reaction yields are moderate. On the basis of these studies, shorter protocols
for assembling (S,S)-isodityrosine and K-13 are developed.
SCHEME 1
Introduction
The Ullmann-type coupling reaction between aryl halides and
protected tyrosine or related amino acid derivatives is an
interesting subject because its products can be directly used for
assembling a number of natural cyclopeptides bearing a diaryl
ether moiety.1 These compounds include monocyclic tripeptides
such as K-13 and OF4949-I-IV, bicyclic bouvardins, and RP-
664536, as well as complex polycyclic antibiotics such as
vancomycin, teicoplanin, and chloropeptins.1
Since Ullmann-type diaryl ether formation is a well-
established transformation process, a key problem for its
application to tyrosine derivatives is how to avoid the possible
racemization of their amino acid moiety. Indeed, the conven-
tional reaction conditions (∼170 °C) are almost certain to
racemize amino acids. Initial attempts to couple two tyrosine
derivatives under these conditions gave only 1.5% yield of the
desired product.2 In 1988 Schmidt et al.3 reported that if
electron-deficient p-bromobenzaldehyde 1 (Scheme 1) was used,
coupling with a tyrosine derivative 4 in the presence of CuO
worked at 130 °C, affording the corresponding diaryl ether in
good yield. Soon after that, Boger and Yohannes4 and Rama
Rao et al.5 discovered that similar results could be obtained when
two other electron-deficient aryl halides, tert-butyl p-iodoben-
zoate 2 and p-nitro-m-bromobenzaldehyde, were employed.
However, coupling reactions between phenylalanine-derived aryl
iodides 3 and tyrosine derivatives 4 failed to give any desired
(1) For reviews, see (a) Rao, A. V. R.; Gurjar, M. K.; Reddy, G. K. L.;
Rao, A. S. Chem. ReV. 1995, 95, 2135. (b) Zhu, J. Synlett 1997, 133. (c)
Nicolaou, K. C.; Boddy, C. N. C.; Bra¨se, S.; Winssinger, N. Angew. Chem.,
Int. Ed. 1999, 38, 2096.
(2) (a) Sano, S.; Ikai, K.; Katayama, K.; Takesako, K.; Nakamura, T.;
Obayashi, A.; Ezure, Y.; Enomoto, H. J. Antibiot. 1986, 39, 1685. (b)
Yasuzawa, T.; Shirahata, K.; Sano, H. J. Antibiot. 1987, 40, 455.
(3) Schmidt, U.; Weller, D.; Holder, A.; Lieberknecht, A. Tetrahedron
Lett. 1988, 29, 3227.
(4) (a) Boger, D. L.; Yohannes, D. Tetrahedron Lett. 1989, 30, 2053.
(b) Boger, D. L.; Yohannes, D. J. Org. Chem. 1989, 54, 2498.
(5) Rama Rao, A. V.; Chakraborty, T. K.; Reddy, K. L.; Rao, A. S.
Tetrahedron Lett. 1992, 33, 4799.
10.1021/jo0606960 CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/03/2006
5268
J. Org. Chem. 2006, 71, 5268-5273

Mild and Nonracemizing Diaryl Ether Formation
products.6a This problem might result from the poor reactivity
of the aryl iodides 3, which resulted in the need for a longer
synthetic sequence for asymmetric elaboration of the required
amino acid units in subsequent conversions to target mole-
cules.1,3-6
TABLE 1. Coupling of 4-Iodophenylacetone and L-Tyrosine
Derivatives Catalyzed by 10 Mol % CuI and 30 Mol %
N,N-Dimethylglycinea
Mild coupling reaction conditions could provide a solution
to the above problem. Toward this goal, Nicolaou et al.7
developed a synthetic technology in which a triazene unit was
placed ortho to a leaving group on the aromatic ring to provide
an ortho substitution effect. Through this modification they
observed that the reaction between aryl halides and L-tyrosine
derivatives proceeded smoothly at 80 °C. Recently, we8a and
other groups9,10 have revealed that some special ligands could
promote Ullmann-type diaryl ether formation, leading to this
transformation complete at 90-130 °C. By combination of the
ligand effect and a newly discovered ortho substitution effect
caused by the acetoamido groups, we found that CuI-catalyzed
diaryl ether synthesis between L-phenylalanine-derived aryl
halides and L-tyrosine derivatives took place at room temper-
ature.11 However, for completion of the target natural products,
a drawback for Nicolaou’s and our processes is the requirement
to remove the N-containing ortho substituents or transform them
into other functional groups via diazotization.7,11 Consequently,
a mild and nonracemizing method for coupling general L-
phenylalanine-derived aryl halides and L-tyrosine derivatives is
still required.
entry
phenol
R
R′
R′′
product
yieldb (%)/eec (%)
1
2
3
4
5
6
7
8
9
7a
7b
7a
7a
7c
7d
7e
7f
Boc
Cbz
Boc
Boc
Tr
Bn
Bn
Bn
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
8a
8b
8a
8a
8c
8d
8e
8f
92/6
88/6
60/64d
40/50e
92/>99
96/>97
86/>98
70/>88
0/-
H
Bn
Me
H
H
H
7g
7h
7i
Me
Boc
Cbz
8g
8a
8b
10
11
60/>97f
53/>98f
H
H
a Reaction conditions: aryl iodide 6 (1 mmol), phenol 7 (1.5 mmol),
CuI (0.1 mmol), N,N-dimethylglycine hydrochloride salt (0.3 mmol), Cs2CO3
(2.1 mmol), dioxane (2 mL), 90 °C, 15 h. b Isolated yield. c Ee value was
determined by chiral HPLC. d Cs2CO3 (0.6 mmol) was used. e CsF (2.1
mmol) was used. f The product was isolated after esterification.
protected amino acids could be inert to these reaction conditions,
thereby giving a chance to develop a useful method for coupling
general L-phenylalanine-derived aryl halides and L-tyrosine
derivatives. With this idea in mind, a reaction of 4-iodophenyl-
acetone 6 with N-Boc-L-tyrosine methyl ester 7a under the
catalysis of CuI/N,N-dimethylglycine at 90 °C was conducted.
As expected, coupling product 8a was isolated in 92% yield
(Table 1, entry 1). However, after measuring its rotation we
disappointedly found that racemization had occurred almost
completely. Using N-Cbz-L-tyrosine methyl ester 7b gave a
similar result (entry 2). To minimize the racemization, we
attempted to reduce the dosage of Cs2CO3 to 0.6 equiv or
employ less basic CsF as a base. In these cases improved results
were observed, but partial racemization still took place as
evidenced from moderate ee values determined (entries 3 and
4).
Considering that N-alkyl groups are poorer substituents for
stabilizing adjacent carbanions compared with N-alkoxycarbonyl
groups, we next tried to change the N-protecting groups of
tyrosine to avoid the racemization. After some experimentation,
it was found that N-trityl-L-tyrosine methyl ester 7c gave the
desired coupling product 8c in 92% yield without any racem-
ization (entry 5). Similar results were observed in cases of N,N-
dibenzyl- and N-benzyl-N-methyl-l-tyrosine methyl esters (7d
or 7e) as the substrates (entries 6 and 7). However, partial
racemization was noticed when N-benzyl-l-tyrosine methyl ester
7f was used (entry 8), while N-methyl-l-tyrosine methyl ester
7g gave no coupling product (entry 9). These results indicated
that the bulkiness of the N-protecting groups also played a role
in this reaction.
Results and Discussion
Since our reaction temperature for CuI/N,N-dimethylglycine-
catalyzed coupling of aryl halides and phenols was relatively
low,8a we envisaged that the asymmetric centers of some
(6) (a) Boger, D. L.; Yohannes, D. J. Org. Chem. 1990, 55, 6000. For
related studies, see (b) Boger, D. L.; Yohannes, D. J. Org. Chem. 1991,
56, 1763. (c) Boger, D. L.; Nomoto, Y.; Teegarden, B. R. J. Org. Chem.
1993, 58, 1425. (d) Boger, D. L.; Yohannes, D.; Zhou, J.; Patane, M. A. J.
Am. Chem. Soc. 1993, 115, 3420. (e) Boger, D. L.; Zhou, J. J. Am. Chem.
Soc. 1995, 117, 7364.
(7) (a) Nicolaou, K. C.; Boddy, C. N. C.; Natarajan, S.; Yue, T.-Y.; Brase,
S.; Ramanjulu, J. M. J. Am. Chem. Soc. 1997, 119, 3421. (b) Nicolaou, K.
C.; Li, H.; Boddy, C. N. C.; Ramanjulu, J. M.; Yue, T.-Y.; Natarajan, S.;
Chu, X.-J.; Bra¨se, S.; Ramanjulu, J. M. Ru¨bsam, F. Chem. Eur. J. 1999, 5,
2584.
(8) (a) Ma, D.; Cai, Q. Org. Lett. 2003, 5, 3799. For related studies, see
(b) Ma, D.; Zhang, Y.; Yao, J.; Wu, S.; Tao, F. J. Am. Chem. Soc. 1998,
120, 12459. (c) Ma, D.; Xia, C. Org. Lett. 2001, 3, 2583. (d) Ma, D.; Cai,
Q.; Zhang, H. Org. Lett. 2003, 5, 2453. (e) Pan, X.; Cai, Q.; Ma, D. Org.
Lett. 2004, 6, 1809. (f) Ma, D.; Cai, Q. Synlett 2004, 1, 128. (g) Zhu, W.;
Ma, D. Chem. Commun. 2004, 888. (h) Ma, D.; Liu, F. Chem. Commun.
2004, 1934. (i) Zhang, H.; Cai, Q.; Ma, D. J. Org. Chem. 2005, 70, 5164.
(j) Zhu, W.; Ma, D. J. Org. Chem. 2005, 70, 2696. (k) Xie, X.; Cai, G.;
Ma, D. Org. Lett. 2005, 7, 4693. (l) Ma, D.; Cai, Q.; Xie, X. Synlett 2005,
1767. (m) Cai, Q.; Zhu, W.; Zhang, H.; Zhang, Y.; Ma, D. Synthesis 2005,
496. (n) Deng, W.; Wang, Y.; Zou, W.; Liu, L.; Guo, Q. Tetrahedron Lett.
2004, 45, 2311. (o) Deng, W.; Zou, Y.; Wang, Y. F.; Liu, F.; Guo, Q. X.
Synlett 2004, 1254. (p) Wang, Z.; Bao, W.; Jiang, Y. Chem. Commun. 2005,
2849.
(9) (a) Cristau, H.-J.; Cellier, P. P.; Hamada, S.; Spindler, J.-F.; Taillefer,
M. Org. Lett. 2004, 6, 913. (b) Buck, E.; Song, Z. J.; Tschaen, D.; Dormer,
P. G.; Volante, R. P.; Reider, P. J. Org. Lett. 2002, 4, 1623. (c) Gujadhur,
R. K.; Bates, C. G.; Venkataraman, D. Org. Lett. 2001, 3, 4315. (d) Palomo,
C.; Oiarbide, M.; Lopez, R.; Gomez-Bengoa, E. Chem. Commun. 1998,
2091. (e) Marcoux, J.-F.; Doye, S.; Buchwald, S. L. J. Am. Chem. Soc.
1997, 119, 10539. (f) Rao, H.; Jin, Y.; Fu, H.; Jiang, Y.; Zhao, Y. Chem.
Eur. J. 2006, 12, 3636.
Reducing the stability of the carbanion by switching its
neighboring alkoxycarbonyl to carboxylate groups is another
possible approach to minimize the racemization. To this end,
two N-protected amino acids 7h and 7i were checked under
our standard reaction conditions. After coupling with 4-iodophen-
ylacetone 6, their products were treated with iodomethane to
afford esters 8a and 8b, respectively. As expected, excellent ee
values were determined for these two esters. However, the
(10) For reviews about recent progress on Ullmann-type reactions, see
(a) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400. (b)
Kunz, K.; Scholz, U.; Ganzer, D. Synlett 2003, 15, 2428. (c) Beletskaya, I.
P.; Cheprakov, A. V. Coord. Chem. ReV. 2004, 248, 2337.
(11) Cai, Q.; Zou, B.; Ma, D. Angew. Chem., Int. Ed. 2006, 45, 1276.
J. Org. Chem, Vol. 71, No. 14, 2006 5269

Cai et al.
TABLE 2. Coupling Reaction of Aryl Iodides with L-Tyrosine Derivatives Catalyzed by 30 Mol % CuI and 100 Mol % N,N-Dimethylglycinea
a Reaction conditions: iodide (0.5 mmol), phenol (0.75 mmol), CuI (0.15 mmol), N,N-dimethylglycine hydrochloride salt (0.5 mmol), Cs2CO3 (1.5
mmol), dioxane (1 mL), 90 °C. b Isolated yield. c Ee value was determined by chiral HPLC. d Ee value was not determined.
overall yields were not satisfactory (entries 10 and 11), which
implied that the presence of a carboxylate group in the substrates
might slow the CuI-catalyzed coupling reaction.
would allow selective manipulation of individual functionalities
in subsequent transformations.
To demonstrate the synthetic usage of the present method,
we next attempted the total synthesis of two natural products
via the CuI/N,N-dimethylglycine-catalyzed coupling reaction.
The first molecule we studied was (S,S)-isodityrosine 19
(Scheme 2), a naturally occurring amino acid isolated from the
plant wall glycoprotein extensin.12 Since its structure is a key
element for a large class of natural products bearing an
endocyclic diaryl ether, (S,S)-isodityrosine has served as a test
for a number of synthetic methods.3-5,13 Obviously, the most
straightforward and practical approach to it is from two natural
On the basis of the above studies, we concluded that the best
results could be obtained when N-trityl and N,N-dibenzyl (or
N-benzyl for methylated amino acids) amino esters were utilized
as the coupling substrates. To further explore the scope of this
method, other related aryl iodides and phenols were examined.
As summarized in Table 2, it was found that, besides electron-
deficient iodides (entry 1), less reactive aryl iodides bearing an
electron-donating group were also compatible with these reaction
conditions (entries 2 and 3). This observation prompted us to
test the coupling reaction with two phenylalanine-derived aryl
iodides 3a and 3b. We were pleased that their reactions with
simple phenols or even some tyrosine derivatives proceeded
well, providing corresponding diaryl ethers in good yields
(entries 4-8). Noteworthy is that, in products 13 and 14, all
amino and carboxylate groups have different protections, which
(12) (a) Fry, S. C. Biochem. J. 1982, 204, 499. (b) Epistein, L.; Lamport,
D. T. A. Phytochemistry 1984, 23, 1241.
(13) For recent examples, see (a) Gupta, A. Sen, S.; Harmata, M.; Pulley,
S. R. J. Org. Chem. 2005, 70, 7422. (b) Jung, M. E.; Lazarova, T. J. Org.
Chem. 1999, 64, 2976. (c) Lygo, B. Tetrahedron Lett. 1999, 40, 1389. (d)
Jørgensen, K. B.; Gautun, O. R. Tetrahedron 1999, 55, 10527.
5270 J. Org. Chem., Vol. 71, No. 14, 2006

Mild and Nonracemizing Diaryl Ether Formation
SCHEME 2
SCHEME 3
aromatic amino acids. Up to this date, this ideal manner was
achieved only by Jung and Lazarova,13b who completed the
synthesis via coupling of an L-phenylalanine-derived arylboronic
acid and an L-tyrosine derivative.
As depicted in Scheme 2, our synthesis for (S,S)-isodityrosine
19 started from carbamate 15, an L-dopa derivative prepared
from L-tyrosine in five steps and 45% overall yield.14 Cleavage
of the Boc group in 15 with TFA followed by reacting the
resultant amine with trityl chloride produced N-trityl amino ester
16. Coupling of this ester with an L-phenylalanine-derived aryl
iodide 17 under the catalysis of CuI/N,N-dimethylglycine
afforded diaryl ether 18 in 86% yield. After removal of the trityl
group in 18 by exposure to TFA, Pd/C-catalyzed hydrogenolysis
was conducted to cleave all benzyl-protecting groups. Upon
treatment with 6 N HCl, (S,S)-isodityrosine was isolated as its
hydrochloride salt. Its analytical data were all identical with
those reported.13 This protocol was similar to that reported by
Jung and Lazarova13b but was more practical because conversion
of aryl iodide to the corresponding arylboronic acid was omitted.
Our next target molecule was K-13, a 17-membered cyclic
peptide isolated from Micromonospora halophytica ssp. exilisia
K-13. It has been shown to be a potent, noncompetitive inhibitor
of angiotensin I-converting enzyme (ACE) and a weak inhibitor
of aminopeptidase B.15 During the past decades, considerable
effects have been directed to its total synthesis and several
successful approaches have been established.5,6,16 Our synthetic
pathway to this molecule is outlined in Scheme 3. CuI/N,N-
dimethylglycine-catalyzed coupling of the L-dopa derivative 16
with the iodide 3b delivered protected isodityrosine 20 in 87%
yield. Selective hydrolysis of the methyl ester in 20 gave rise
to a liberated acid, which was connected with L-tyrosine tert-
butyl ester to furnish peptide 21. Next, treatment of 21 with
TFA removed the trityl and tert-butyl groups, and the resultant
amino acid was subjected to macrocyclization mediated with
DPPA and NaHCO3 in a diluted DMF solution to afford lactam
22. Finally, hydrogenolysis of 22 accompanied by acylation in
methanol containing acetic anhydride provided K-13 in 50%
yield. This protocol took only seven steps from a known
intermediate 15 and gave a 14% overall yield, representing one
of the simplest routes for assembling K-13.
In summary, we have developed a method for elaboration of
enantiopure isodityrosine derivatives via an intermolecular
Ullmann-type coupling reaction between L-tyrosine derivatives
and L-phenylalanine-derived aryl iodides. The key issue is using
N-trityl- or N,N-dibenzyl-protected amino esters as substrates
and N,N-dimethylglycine as a reaction promoter to avoid
racemization and achieve good coupling yields. Its value has
been illustrated by successful applications in the total synthesis
of (S,S)-isodityrosine and K-13. Further applications to assemble
other related molecules and their analogues are in progress and
will be reported in due course.
Experimental Section
General Procedure for CuI/N,N-dimethylglycine-Catalyzed
Coupling Reaction of Aryl Iodides and Phenols. A Schlenk tube
was charged with aryl iodide (0.5 mmol), phenol (0.75 mmol), CuI
(0.15 mmol), N,N-dimethylglycine hydrochloride salt (0.5 mmol),
Cs2CO3 (1.5 mmol), and 2 mL of 1, 4-dioxane, evacuated, and
backfilled with argon. The reaction mixture was stirred at 90 °C
until the conversion was completed as detected by TLC. The
suspension was filtered and the filtrate was concentrated, followed
by column chromatography on silica gel (eluting with 1:100 to 1:5
ethyl acetate/petroleum ether) to provide the desired product.
(S)-3-[4-(4-Acetylphenoxy)phenyl]-2-tert-butoxycarbonylami-
nopropionic Acid Methyl Ester 8a. [R]D25 +36.5 (c 0.59, CHCl3);
1H NMR (CDCl3, 300 MHz) δ 7.96 (d, J ) 9.0 Hz, 2H), 7.17 (d,
J ) 9.0 Hz, 2H), 7.01 (d, J ) 9.0 Hz, 2H), 7.00 (d, J ) 9.0 Hz,
2H), 5.06 (d, J ) 7.2 Hz, 1H), 4.64 (m, 1H), 3.74 (s, 3H), 3.18 (m,
2H), 2.58 (s, 3H), 1.43 (s, 9H); 13C NMR (CDCl3, 300 MHz) δ
(14) Chen, C.; Zhu, Y.-F.; Wilcoxen, K. J. Org. Chem. 2000, 65, 2574.
(15) Kase, H.; Kaneko, M.; Yamada, K. J. Antibiot. 1987, 40, 450.
(16) (a) Bigot, A.; Bois-Choussy, M.; Zhu, J. Tetrahedron Lett. 2000,
41, 4573. (b) Janetka, J. W.; Rich, D. H. J. Am. Chem. Soc. 1997, 119,
6488. (c) Pearson, A. J. Lee, K. J. Org. Chem. 1994, 59, 2304. (d)
Nishiyama, S.; Suzuki, Y.; Yamamura, S. Tetrahedron Lett. 1989, 30, 379.
(e) Evans, D. A. Ellmann, J. A. J. Am. Chem. Soc. 1989, 111, 1063.
J. Org. Chem, Vol. 71, No. 14, 2006 5271

Cai et al.
196.3, 172.0, 161.6, 154.8, 154.2, 132.4, 131.6, 130.6, 130.3, 120.0,
117.0, 79.5, 54.3, 51.9, 37.4, 28.0, 21.1; ESI-MS m/z 436.2 (M +
Na)+; HRMS calcd for C23H27NO6Na (M + Na)+ 436.1750, found
436.1731.
6.90 (m, 4H), 3.80 (s, 3H), 3.54 (m, 1H), 3.05 (s, 3H), 2.92 (d, J
) 6.0 Hz, 2H), 2.62 (d, J ) 10.2 Hz, 1H); 13C NMR (CDCl3, 300
MHz) δ 174.9, 157.4, 155.9, 150.4, 145.9, 131.6, 131.0, 128.9,
127.8, 126.4, 120.7, 117.5, 114.9, 71.1, 58.4, 55.7, 51.4, 41.6; IR
(film) 3316, 3057, 3000, 1737, 1499 cm-1; ESI-MS m/z 566.2 (M
+ Na)+; HRMS calcd for C36H33NO4Na (M + Na)+ 566.2301,
found 566.2280.
(S)-2-Dibenzylamino-3-(4-p-tolyloxyphenyl)propionic Acid
Methyl Ester 11. [R]D25 -40.8 (c 0.65, CHCl3); 1H NMR (CDCl3,
300 MHz) δ 7.13 (m, 12H), 6.85 (m, 6H), 5.20 (d, J ) 12.0 Hz,
1H), 3.89 (d, J ) 14.1 Hz, 2H), 3.65 (s, 3H), 3.57 (m, 1H), 3.48
(d, J ) 14.1 Hz, 2H), 2.91 (m, 2H), 2.27 (s, 3H); 13C NMR (CDCl3,
300 MHz) δ 172.8, 155.9, 155.1, 139.2, 132.7, 132.5, 130.6, 130.1,
128.7, 128.1, 126.9, 118.6, 118.4, 62.2, 54.3, 51.2, 34.9, 20.7; ESI-
MS m/z 466.2 (M + H)+; HRMS calcd for C31H32NO3 (M + H)+
466.2377, found 466.2370.
(S)-3-(4-{4-[(S)-2-Methoxycarbonyl-2-tritylamino]ethyl}phen-
oxy)phenyl)-2-(tritylamino)propionic Acid Methyl Ester 12.
[R]D25 +71.9 (c 0.99, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 7.42
(m, 13H), 7.25 (m, 21H), 6.92 (d, J ) 7.2 Hz, 2H), 3.58 (m, 2H),
3.05 (s, 6H), 2.93 (m, 4H); 13C NMR (CDCl3, 300 MHz) δ 174.8,
156.1, 145.8, 132.3, 131.0, 128.7, 127.7, 126.3, 118.5, 71.0, 58.3,
51.3, 41.5; IR (film) 3057, 3031, 1737, 1598 cm-1; ESI-MS m/z
879.4 (M + Na)+; HRMS calcd for C58H52N2O5Na (M + Na)+
879.3768, found 879.3749.
(S)-3-[4-(4-Acetylphenoxy)phenyl]-2-benzyloxycarbonylami-
nopropionic Acid Methyl Ester 8b. [R]D25 +38.7 (c 0.58, CHCl3);
1H NMR (CDCl3, 300 MHz) δ 7.95 (d, J ) 9.0 Hz, 2H), 7.39 (m,
5H), 7.13 (d, J ) 9.0 Hz, 2H), 6.97 (m, 4H), 5.27 (m, 1H), 5.11
(m, 2H), 4.65 (m, 1H), 3.74 (s, 3H), 3.18 (m, 2H), 2.57 (s, 3H);
13C NMR (CDCl3, 300 MHz) δ 196.7, 171.8, 161.7, 155.5, 154.5,
136.1, 132.0, 131.9, 130.8, 130.5, 128.5, 128.2, 128.1, 120.1, 117.3,
67.0, 54.7, 52.4, 37.5, 26.4; IR (film) 3414, 2970, 1749, 1712, 1675,
1596 cm-1; ESI-MS m/z 470.1 (M + Na)+; HRMS calcd for C26H25-
NO6Na (M + Na)+ 470.1574, found 470.1573.
(S)-3-[4-(4-Acetylphenoxy)phenyl]-2-(tritylamino)propionic Acid
25
1
Methyl Ester 8c. [R]D +57.7 (c 1.0, CHCl3); H NMR (CDCl3,
300 MHz) δ 7.94 (d, J ) 8.4 Hz, 2H), 7.43 (m, 6H), 7.20 (m,
11H), 7.00 (m, 4H), 3.61 (m, 1H), 3.06 (s, 3H), 2.97 (m, 2H), 2.65
(d, J ) 11.1 Hz, 1H), 2.57 (s, 3H); 13C NMR (CDCl3, 300 MHz)
δ 196.8, 174.8, 162.2, 154.3, 145.9, 134.0, 131.9, 131.5, 130.7,
128.9, 128.2, 127.9, 126.7, 126.5, 120.1, 117.2, 71.1, 58.3, 51.4,
41.7, 26.5; IR (film) 3317, 3057, 3021, 1738, 1681, 1594 cm-1
;
ESI-MS m/z 578.3 (M + Na)+; HRMS calcd for C37H33NO4Na
(M + Na)+ 578.2302, found 578.2301.
(S)-3-[4-(4-Acetylphenoxy)phenyl]-2-dibenzylaminopropion-
ic Acid Methyl Ester 8d. [R]D25 -37.6 (c 0.53, CHCl3); 1H NMR
(CDCl3, 300 MHz) δ 7.96 (d, J ) 8.7 Hz, 2H), 7.29 (m, 10H),
7.02 (m, 4H), 6.95 (d, J ) 8.4 Hz, 2H), 3.98 (d, J ) 14.1 Hz, 1H),
3.77 (s, 3H), 3.70 (t, J ) 7.5 Hz, 1H) 3.57 (d, J ) 14.1 Hz, 2H),
3.15 (dd, J ) 14.1, 6.6 Hz, 1H), 3.00 (d, J ) 14.1, 8.7 Hz, 1H),
2.58 (s, 3H); 13C NMR (CDCl3, 300 MHz) δ 196.4, 172.4, 162.0,
153.8, 139.2, 134.8, 131.8, 131.5, 131.1, 130.7, 128.8, 126.9, 120.0,
116.7, 61.9, 54.2, 51.0, 34.9, 26.2; IR (film) 3030, 2951, 1732,
1681, 1595 cm-1; ESI-MS m/z 494.2 (M + H)+; HRMS calcd for
C32H32NO4 (M + H)+ 494.2326, found 494.2329.
(S)-3-{4-[4-((S)-2-Dibenzylamino-2-methoxycarbonylethyl)-
phenoxy]phenyl}-2-(tritylamino)propionic Acid Methyl Ester
25
1
13. [R]D +16.8 (c 1.1, CHCl3); H NMR (CDCl3, 300 MHz) δ
7.43 (m, 6H), 7.25 (m, 21H), 6.95 (m, 6H), 3.98 (m, 2H), 3.75 (s,
3H), 3.68 (s, 1H), 3.54 (m, 3H), 3.07 (s, 3H), 2.95 (m, 3H), 2.60
(m, 1H); 13C NMR (CDCl3, 300 MHz) δ 174.8, 172.8, 155.5, 145.8,
139.2, 133.1, 132.1, 131.0, 130.6, 128.8, 128.7, 128.3, 127.8, 127.0,
126.4, 118.7, 118.2, 71.0, 62.2, 58.3, 54.4, 51.3, 51.2, 41.5, 35.0;
IR (film) 3059, 3029, 1733, 1601 cm-1; ESI-MS m/z 795.3 (M +
H)+; HRMS calcd for C53H51N2O5 (M + H)+ 795.3792, found
795.3782.
(S)-3-[4-(4-Acetylphenoxy)phenyl]-2-(benzylmethylamino)-
25
propionic Acid Methyl Ester 8e. [R]D -39.2 (c 0.73, CHCl3);
(S)-3-{4-[4-((S)-2-Benzyloxycarbonyl-2-dibenzylaminoethyl)-
phenoxy]phenyl}-2-dibenzylaminopropionic Acid Methyl Ester
1H NMR (CDCl3, 300 MHz) δ 7.95 (d, J ) 9.0 Hz, 2H), 7.29 (m,
7H), 7.0 (d, J ) 8.4 Hz, 2H), 6.97 (d, J ) 8.4 Hz, 2H), 3.84 (d, J
) 14.1 Hz, 1H), 3.72 (s, 3H), 3.62 (m, 1H), 3.60 (m, 1H), 3.15
(dd, J ) 14.1, 7.8 Hz, 1H), 2.98 (d, J ) 14.1, 6.3 Hz, 1H), 2.57 (s,
3H), 2.33 (s, 3H); 13C NMR (CDCl3, 300 MHz) δ 196.4, 171.9,
162.0, 153.5, 138.8, 134.7, 131.4, 130.6, 130.4, 128.4, 128.0, 126.9,
119.8, 116.7, 66.7, 58.7, 50.9, 37.5, 34.8, 26.2; IR (film) 1732,
1681, 1595 cm-1; ESI-MS m/z 418.1 (M + H)+; HRMS calcd for
C26H28NO4 (M + H)+ 418.2013, found 418.2024.
25
1
14. [R]D -57.1 (c 0.85, CHCl3); H NMR (CDCl3, 300 MHz) δ
7.39 (m, 5H), 7.20 (m, 20H), 5.30 (m, 2H), 3.96 (m, 4H), 3.75 (s,
3H), 3.67 (m, 2H), 3.52 (m, 4H), 3.06 (m, 4H); 13C NMR (CDCl3,
300 MHz) δ 172.8, 172.1, 155.9, 155.8, 139.2, 139.1, 132.9, 132.8,
130.6, 128.7, 128.6, 128.5, 128.3, 128.2, 127.0, 126.9, 118.5, 118.4,
66.1, 62.3, 62.2, 54.4, 54.3, 51.2, 35.0, 34.9; IR (film) 3063, 3030,
1732, 1603, 1502 cm-1; ESI-MS m/z 809.4 (M + H)+; HRMS calcd
for C54H53N2O5 (M + H)+ 809.3949, found 809.3953.
(S)-3-[4-(4-Acetylphenoxy)phenyl]-2-benzylaminopropionic
(S)-3-(4-Benzyloxy-3-hydroxyphenyl)-2-(tritylamino)propi-
onic Acid Benzyl Ester 16. A solution of 15 (6.0 g, 12.6 mmol)
in 75 mL of CH2Cl2 and 25 mL of TFA was stirred for 4 h at room
temperature before it was concentrated to dryness. The residue was
dissolved in 30 mL of DMF. TrCl (4.2 g, 15.1 mmol) and Et3N
(5.3 mL, 37.8 mmol) were added at 0 °C. The mixture was stirred
for 4 h before it was partitioned between EtOAc and water. The
aqueous phase was extracted with EtOAc. The combined organic
layers were washed with water and brine, dried over Na2SO4, and
concentrated in vacuo. Flash chromatography of the residue afforded
6.6 g (85%) of 16: [R]D25 +37.7 (c 0.63, CHCl3); 1H NMR (CDCl3,
300 MHz) δ 7.39 (m, 11H), 7.15 (m, 12H), 6.93 (m, 2H), 6.52 (m,
2H), 6.49 (m, 1H), 5.52 (s, 1H), 4.97 (s, 2H), 4.44 (d, J ) 12.6
Hz, 1H), 4.19 (d, J ) 12.6 Hz, 1H), 3.52 (m, 1H), 2.90 (dd, J )
13.5, 6.3 Hz, 1H), 2.76 (dd, J ) 13.5, 7.5 Hz, 1H), 2.60 (d, J )
10.2 Hz, 1H); 13C NMR (CDCl3, 300 MHz) δ 174.4, 145.8, 145.5,
144.6, 136.3, 135.2, 130.8, 128.7, 128.6, 128.5, 128.2, 128.1, 128.0,
127.7, 127.6, 126.3, 121.1, 116.1, 111.8, 71.0, 66.3, 58.3, 41.7; IR
(film) 3528, 3059, 1732, 1594, 1508 cm-1; ESI-MS m/z 642.3 (M
+ Na)+; HRMS calcd for C42H37NO4Na (M + Na)+ 642.2615,
found 642.2603.
25
1
Acid Methyl Ester 8f. [R]D +11.8 (c 0.56, CHCl3); H NMR
(CDCl3, 300 MHz) δ 7.95 (d, J ) 9.0 Hz, 2H), 7.29 (m, 5H), 7.21
(d, J ) 9.0 Hz, 2H), 6.97 (m, 4H), 3.87 (d, J ) 12.9 Hz, 1H), 3.68
(s, 3H), 3.63 (m, 1H), 3.54 (t, J ) 6.9 Hz, 1H), 2.96 (m, 2H), 2.57
(s, 3H); 13C NMR (CDCl3, 300 MHz) δ 196.6, 174.8, 162.0, 154.1,
139.5, 133.8, 131.8, 130.8, 130.5, 128.3, 128.1, 127.0, 120.0, 117.1,
61.9, 51.9, 51.6, 38.9, 26.3; IR (film) 3337, 1735, 1677, 1597 cm-1
;
ESI-MS m/z 404.2 (M + H)+; HRMS calcd for C25H26NO4 (M +
H)+ 404.1856, found 404.1852.
(S)-3-[4-(4-Cyanophenoxy)phenyl]-2-(tritylamino)propionic
25
1
Acid Methyl Ester 9. [R]D +59.6 (c 0.85, CHCl3); H NMR
(CDCl3, 300 MHz) δ 7.60 (d, J ) 8.7 Hz, 2H), 7.40 (m, 6H), 7.20
(m, 11H), 7.00 (m, 4H), 3.60 (m, 1H), 3.07 (s, 3H), 2.98 (d, J )
6.6 Hz, 2H), 2.64 (d, J ) 10.8 Hz, 1H); 13C NMR (CDCl3, 300
MHz) δ 174.7, 161.8, 153.6, 145.9, 134.6, 134.2, 131.7, 128.8,
127.9, 126.5, 120.2, 118.9, 117.9, 105.8, 71.1, 58.2, 51.4, 41.6; IR
(film) 3318, 3057, 1737, 1597 cm-1; ESI-MS m/z 561.2 (M + Na)+;
HRMS calcd for C36H30N2O3Na (M + Na)+ 561.2149, found
561.2162.
(S)-3-[4-(4-Methoxyphenoxy)phenyl]-2-(tritylamino)propion-
ic Acid Methyl Ester 10. [R]D25 +59.1 (c 0.61, CHCl3); 1H NMR
(CDCl3, 300 MHz) δ 7.41 (m, 6H), 7.20 (m, 11H), 6.99 (m, 2H),
(S)-3-(4-Benzyloxy-3-{4-[(S)-2-benzyloxycarbonyl-2-(trityl-
amino)ethyl]phenoxy}phenyl)-2-(tritylamino)propionic Acid Ben-
5272 J. Org. Chem., Vol. 71, No. 14, 2006

Mild and Nonracemizing Diaryl Ether Formation
zyl Ester 18. A mixture of 16 (310 mg, 0.5 mmol), 17 (467 mg,
0.75 mmol), CuI (28.5 mg, 0.15 mmol), N,N-dimethylglycine
hydrochloride (70 mg, 0.5 mmol), and Cs2CO3 (489 mg, 1.5 mmol)
in 2 mL of 1,4-dioxane was stirred for 30 h at 90 °C. The mixture
was filtered through Celite and washed with EtOAc. The filtrate
was concentrated in vacuo and the residue was chromatographed
to afford 479 mg (86%) of 18: [R]D +40.3 (c 0.6, CHCl3); H
NMR (CDCl3, 300 MHz) δ 7.43 (m, 14H), 7.22 (m, 29H), 6.99
(m, 5H), 6.88 (m, 2H), 6.78 (m, 2H), 5.05 (s, 2H), 4.52 (m, 2H),
4.44 (m, 2H), 4.27 (m, 2H), 3.57 (m, 2H), 2.92 (m, 4H), 2.59 (m,
2H); 13C NMR (CDCl3, 300 MHz) δ 174.4, 174.2, 157.2, 149.5,
145.9, 145.8, 145.1, 137.0, 135.3, 131.0, 130.9, 130.8, 128.8, 128.7,
128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.0,
125.3, 125.0, 123.5, 121.2, 116.6, 116.2, 115.1, 71.1, 71.0, 70.9,
66.4, 66.3, 58.3, 58.2, 41.5, 41.3; IR (film) 3059, 1734, 1596, 1506
cm-1; ESI-MS m/z 1137.4 (M + Na)+; HRMS calcd for C77H66N2O6-
Na (M + Na)+ 1137.4813, found 1137.4811.
(S,S)-Isodityrosine 19. A solution of 18 (111 mg, 0.1 mmol) in
2 mL of CH2Cl2/TFA (1:1) was stirred for 2 h at room temperature
and then concentrated in vacuo. The reaction was quenched by
adding aqueous NaHCO3. The aqueous phase was extracted with
EtOAc. The combined organic layers were washed with brine, dried
over Na2SO4, and concentrated in vacuo. Flash chromatography of
the residue afforded the crude amine.
The above amine was dissolved in 1 mL of MeOH, and then
Pd/C (30 mg) was carefully added to the solution. After being stirred
for 24 h under H2 atmosphere, the mixture was filtered through
Celite. The filtrate was concentrated to dryness in vacuo. The
residue was added with 6 N HCl (2 mL) and stirred for 5 h at 60
°C. The mixture was extracted with EtOAc. The aqueous phase
was concentrated in vacuo to afford the hydrochloride salt of 19
(39 mg, 90%): [R]D25 -24.2 (c 0.2, MeOH); 1H NMR (D2O, 300
MHz) δ 7.18 (d, J ) 8.4 Hz, 2H), 7.00 (br s, 2H), 6.89 (m, 3H),
4.14 (m, 2H), 3.10 (m, 4H); IR (film) 3413, 3100, 1740, 1639,
1508 cm-1; ESI-MS m/z 361.1 (M + H)+; HRMS calcd for
C18H21N2O6 (M + H)+ 361.1395, found 361.1402.
The aqueous phase was extracted with EtOAc. The combined
organic layers were washed with brine, dried over Na2SO4, and
concentrated in vacuo. Flash chromatography of the residue afforded
25
404 mg (88%) of 21: [R]D +1.7 (c 0.62, CHCl3); 1H NMR
(CDCl3, 300 MHz) δ 7.39 (m, 7H), 7.25 (m, 30H), 6.93 (m, 7H),
6.58 (d, J ) 8.1 Hz, 2H), 5.05 (s, 2H), 4.65 (m, 1H), 4.48 (d, J )
12.0 Hz, 1H), 4.30 (d, J ) 12.0 Hz, 1H), 3.52 (m, 6H), 3.28 (m,
1H), 2.80 (m, 6H), 2.60 (m, 1H), 1.42 (s, 9H); 13C NMR (CDCl3,
300 MHz) δ 174.3, 172.2, 170.7, 156.6, 155.0, 149.2, 145.8, 145.3,
138.6, 136.9, 135.2, 133.9, 130.9, 130.4, 128.7, 128.6, 128.5, 128.4,
128.3, 128.2, 128.1, 127.8, 127.7, 127.1, 127.0, 126.3, 125.8, 123.1,
117.0, 115.3, 115.0, 82.2, 71.0, 70.9, 66.4, 63.6, 58.2, 54.4, 54.2,
41.3, 37.7, 31.2, 27.9; ESI-MS m/z 1182.4 (M + H)+; HRMS calcd
for C78H75N3O8Na (M + Na)+ 1204.5446, found 1204.5434.
(9S,12S,15S)-4-Benzyloxy-15-dibenzylamino-12-(4-hydroxy-
benzyl)-11,14-dioxo-2-oxa-10,13-diazatricyclo[15.2.2.13,7]docosa-
1(20),3(22),4,6,17(21),18-hexaene-9-carboxylic Acid Benzyl Ester
22. A solution of 21 (185 mg, 0.16 mmol) in 2 mL of CH2Cl2/
TFA (1:1) was stirred for 2 h at room temperature and then
concentrated in vacuo. The residue was dissolved in DMF (32 mL)
before NaHCO3 (80 mg, 0.95 mmol) and DPPA (86.7 mg, 0.32
mmol) were added. After it was stirred for 3 days at 0 °C, the
solution was diluted with 50 mL of EtOAc and water (1:1). The
water phase was extracted with EtOAc (3 × 20 mL). The combined
organic layers were washed with water and brine, dried over Na2-
SO4, and concentrated in vacuo. Flash chromatography afforded
22 (81 mg, 60%): [R]D25 -72.0 (c 0.55, CHCl3); 1H NMR (CHCl3,
300 MHz) δ 7.44 (m, 22H), 7.15 (d, J ) 8.7 Hz, 1H), 7.04 (m,
3H), 6.76 (d, J ) 7.8 Hz, 1H), 6.64 (d, J ) 7.5 Hz, 2H), 6.62 (d,
J ) 8.4 Hz, 1H), 6.15 (dd, J ) 8.7, 1.5 Hz, 1H), 5.96 (d, J ) 1.8
Hz, 1H), 5.77 (d, J ) 6.3 Hz, 1H), 5.54 (d, J ) 5.1 Hz, 1H), 5.10
(m, 4H), 4.35 (m, 1H), 4.17 (d, J ) 14.1 Hz, 2H), 3.99 (m, 1H),
3.68 (d, J ) 14.1 Hz, 2H), 2.86 (m, 4H), 2.72 (m, 3H); 13C NMR
(CHCl3, 300 MHz) 171.0, 170.4, 170.0, 155.2, 154.9, 149.6, 147.5,
139.8, 137.1, 134.8, 133.7, 131.7, 130.4, 129.7, 128.8, 128.7, 128.5,
128.4, 128.3, 127.9, 127.8, 127.2, 127.1, 122.8, 122.3, 121.1, 118.1,
115.5, 115.1, 114.1; IR (film) 3392, 2962, 2926, 1742, 1650, 1508,
1454, 1263, 1216, 1127, 697 cm-1; ESI-MS m/z 886.4 (M + H)+;
HRMS calcd for C55H52N3O7 (M + H)+ 866.3800, found 866.3794.
K-13 (23). To a solution of 22 (20 mg, 0.023 mmol) in 1 mL
methanol were added Pd/C (10 mg) and Ac2O (2.1 µL). The mixture
was stirred under 50 psi of H2 atmosphere for 2 days and then
filtered and evaporated in vacuo. Flash chromatography afforded
23 (6 mg, 50%): [R]D25 -6.4 (c 0.48, MeOH); 1H NMR (MeOH-
d4, 300 MHz) δ 7.29 (dd, J ) 8.4, 2.4 Hz, 1H), 7.05 (dd, J ) 8.1,
2.7 Hz, 1H), 6.97 (dd, J ) 8.0, 2.1 Hz, 1H), 6.93 (d, J ) 8.1 Hz,
2H), 6.74 (d, J ) 8.4 Hz, 1H), 6.68 (dd, J ) 1.8, 8.4 Hz, 1H), 6.64
(dd, J ) 8.4, 3.0 Hz, 1H), 6.57 (d, J ) 8.4 Hz, 2H), 6.33 (d, J )
1.5 Hz, 1H); 4.44 (dd, J ) 9.6, 3.0 Hz, 1H), 4.33 (dd, J ) 12.0,
5.1 Hz, 1H), 4.10 (t, J ) 6.0 Hz, 1H), 3.10 (dd, J ) 15.0, 3.0 Hz),
3.05 (m, 1H), 2.96 (m, 4H), 2.01 (s, 3H); 13C NMR (MeOH-d4,
300 MHz) 173.2, 172.6, 172.2, 158.5, 157.5, 148.3, 133.2, 132.4,
132.3, 131.6, 130.4, 128.5, 125.6, 122.3, 121.1, 119.0, 117.9, 116.2,
57.6, 56.1, 53.8, 39.5, 39.0, 36.6, 22.7; IR (film) 3400 (br), 1740,
1670, 1590, 1516 cm-1; ESI-MS m/z 548.3 (M + H)+; HRMS calcd
for C29H30N3O8 (M + H)+ 548.2033, found 548.2027.
25
1
(S)-3-{4-Benzyloxy-3-[4-(S)-2-dibenzylamino-2-methoxycar-
bonylethyl]phenoxy}phenyl}-2-(tritylamino)propionic Acid Ben-
zyl Ester 20. A mixture of 16 (310 mg, 0.5 mmol), 3b (364 mg,
0.75 mmol), CuI (28.5 mg, 0.15 mmol), N,N-dimethylglycine
hydrochloride (70 mg, 0.5 mmol), and Cs2CO3 (489 mg, 1.5 mmol)
in 2 mL of 1,4-dioxane was stirred for 30 h at 90 °C. The mixture
was filtered through Celite and washed with EtOAc. The filtrate
was concentrated in vacuo, and the residue was chromatographed
25
1
to afford 425 mg (87%) of 20: [R]D -9.0 (c 0.78, CHCl3); H
NMR (CDCl3, 300 MHz) δ 7.39 (m, 10H), 7.23 (m, 24H), 7.00
(m, 2H), 6.97 (m, 6H), 5.08 (s, 2H), 4.48 (d, J ) 12.0 Hz, 1H),
4.23 (d, J ) 12.0 Hz, 1H), 3.97 (d, J ) 14.1 Hz, 2H), 3.67 (s, 3H),
3.66 (m, 1H), 3.55 (m, 3H), 3.10 (m, 1H), 2.92 (m, 1H), 2.82 (m,
2H), 2.60 (m, 1H); 13C NMR (CDCl3, 300 MHz) δ 174.1, 172.7,
156.6, 149.2, 145.8, 145.3, 139.2, 136.9, 135.2, 131.9, 130.9, 130.3,
128.7, 128.6, 128.4, 128.3, 128.2, 128.1, 128.0, 127.8, 127.7, 127.0,
126.9, 126.3, 125.8, 123.0, 116.8, 114.9, 71.0, 70.9, 66.3, 62.4,
58.1, 51.1, 41.3, 35.0; ESI-MS m/z 977.4 (M + H)+; HRMS calcd
for C66H61N2O6 (M + H)+ 977.4524, found 977.4522.
(S)-3-[4-Benzyloxy-3-(4-{(S)-2-[(S)-1-tert-butoxycarbonyl-2-
(4-hydroxy-phenyl)ethylcarbamoyl]-2-dibenzylaminoethyl}-
phenoxy)phenyl]-2-(tritylamino)-propionic Acid Benzyl Ester
21. A mixture of 20 (500 mg, 0.51 mmol), LiOH (64 mg, 1.5
mmol), THF (3 mL), MeOH (1 mL), and H2O (1 mL) was stirred
at 0 °C for 30 min. After the solution was treated with 1 N HCl to
adjust the pH to about 2, it was extracted with EtOAc. The organic
layers were washed with brine, dried over Na2SO4, and concentrated
in vacuo to give crude acid (374 mg, 76%), which was dissolved
in DMF (9 mL). To this solution were added sequentially l-tyrosine
tert-butyl ester (138 mg, 0.58 mmol), HOAt (105 mg, 0.77 mmol),
EDCI (148 mg, 0.77 mmol), and DIPEA (0.27 mL, 1.54 mmol) at
0 °C. The mixture was stirred for 3 h at 0 °C and 11 h at room
temperature before it was partitioned between EtOAc and water.
Acknowledgment. We are grateful to the Chinese Academy
of Sciences, National Natural Science Foundation of China
(Grants 20321202 and 20572119) and the Science and Technol-
ogy Commission of Shanghai Municipality (Grants 02JC14032
and 03XD14001) for their financial support.
1
Supporting Information Available: Copies of H NMR and
13C NMR spectra for all new products. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO0606960
J. Org. Chem, Vol. 71, No. 14, 2006 5273